Use of Monte Carlo simulation to estimate and optimize treatment regimens for antibiotic administration in general surgery
- Author:
Xin CHEN
1
Author Information
- Publication Type:Journal Article
- Keywords: Dose-dependent; Imipenem; PK/PD, Monte Carlo simulation; Rational drug therapy; Time-dependent
- From: Chinese Pharmaceutical Journal 2013;48(4):309-313
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE: To estimate and optimize the dosing regimens of antibiotics in general surgery with the utilization of Monte Carlo simulation (MCS) based on PK/PD. METHODS: The mean treatment duration(MTD) of different dosing regimens were gathered from clinical cases. MCS model was used to simulate the regimens against Escherichia coli, Klebsiella pneumonius, Acinetobacter baumannii and Pseudomonas aeruginosa, respectively. RESULTS: The CFRs of 500 mg TID, 500 mg QID, 1.0 g BID and 1.0 g TID imipenem against Escherichia coli and Klebsiella pneumonius were greater than that of 500 mg BID (100%; 99%). Correspondingly, MTD of those regimens achieved CFR 100% were shorter than that of 500 mg BID. The CFRs of imipenem against Acinetobacter baumannii and Pseudomonas aeruginosa were all less than 90%, the CFRs of 200 mg BID, 400 mg QD levofloxacin and 200 mg QD, 200 mg BID, 400 mg QD amikacin were all below 90%. CONCLUSION: The 5 dosing regimens of imipenem were all effective against Escherichia coli and Klebsiella pneumonius. In consideration of pharmaceutical economics, 500 mg TID was the most rational choice. It suggested drug resistance and promoted combined medication that the CFRs of imipenem against Acinetobacter baumannii and Pseudomonas aeruginosa failed to achieve 90%. Drug resistance was also demonstrated by low CFR values of levofloxacin and amikacin treatments. Nevertheless, results of MCS showed inversely proportional between MTD and CFRs, and displayed obvious dose-dependent characteristics of levofloxacin and amikacin. On the purpose of achieving effective concentration, sufficient dose once a day of levofloxacin and amikacin medication were recommend.
